Assessing amyloid-β, tau, and glial features in Lothian Birth Cohort 1936 participants post-mortem

Decline in cognitive function is one of the most feared aspects of ageing. We are yet to fully understand why some people age with relatively intact cognition, while others experience subtle cognitive decline or even dementia. The Lothian Birth Cohort 1936(LBC1936) was established to investigate lifetime cognitive changes, with data collectedat 11 years of age and again at 70 years old, onwards. The individuals have been extensively characterised in terms of genetics, cognitive function, and biomedical,psychological, and lifestyle factors. This pilot study characterises and quantifies morphological and pathological features of the first nine donated brains from this cohort.Specifically, we have analysed amyloid-beta (Aβ), phosphorylated tau, microglia andastrocyte levels in five brain regions from nine non-demented LBC1936 participants’ postmortem brain tissue to determine how these factors vary between brain regions. Amyloid-β (Aβ) and phosphorylated tau tangles are hallmarks of Alzheimer's disease, the most prevalent form of dementia, although these have also been described in the brains of some non-demented aged individuals. In both ageing and dementia, immune-related changes are common, including microglia and astrocyte dysfunction. We found that tau tangles and glial cell coverage were highest in the hippocampus, in contrast to Aβ which was more abundant in the neocortex. We anticipate that this cohort will provide invaluable information about brain changes during normal ageing, and act as an age-matched control group for studies investigating neurodegenerative disorders with significant cognitive impairment, such as Alzheimer’s disease.